Biomedical subjects

Manuela Dittmar

Publications and source records attributed to Manuela Dittmar.

11 recordsLinked to original sources

PubMed2007

[Polymorphisms of MICA microsatellites in thyroidal autoimmunity].

BACKGROUND: The autoimmune thyropathies Graves' disease (GD) and Hashimoto's thyroiditis (HT) have multiple genetic and environmental backgrounds. Allele alterations of immune genes might contribute to the development of autoimmunity. PATIENTS AND METHODS: This study determined a triplet short tandem repeat (STR) polymorphism in the transmembrane region of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) of 391 subjects (129 patients with GD, 56 patients with HT, and 206 healthy controls). Five common alleles have been reported for MICA. Genotypes were determined by fragment-length analysis in an ABI PRISM automatic sequencer. RESULTS: The prevalence of the MICA allele A9 was raised in patients with HT compared to controls (22.4% vs. 13.1%; p = 0.016; Fisher's exact test). For MICA, the genotype A5.1/A5.1 occurred more frequently in patients with GD than in controls (24.0% vs. 13.6%, odds ratio [OR] = 2.0, 95% confidence interval [95% CI] = 1.1-3.6; p = 0.018). The genotype MICA A6/A9 was decreased in patients with GD in contrast to controls (1.6% vs. 5.8%, OR = 0.2, 95% CI = 0.6-1.2; p = 0.089). Also, in patients with HT, the genotype A5.1/A9 was increased compared to controls (23.2% vs. 10.7%, OR = 2.5, 95% CI = 1.2-5.4; p = 0.025). CONCLUSION: The genotype MICA A5.1/A5.1 may be regarded as a risk factor for the development of GD. Also, the MICA genotype A5.1/A9 could raise the risk for acquiring HT. Finally, the genotype MICA A6/A9 could be seen as a protective factor against GD.

Adult↗

PubMed2005

Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

CONTEXT: Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them. OBJECTIVE: The objective of this study was to optimize glucocorticoid application in GO. DESIGN: The study design was a randomized trial over 12 wk with 6-month follow-up. SETTING: The study was performed at university joint thyroid and ophthalmic clinics. PATIENTS: Seventy euthyroid out-patients with untreated, active, and severe GO were studied. INTERVENTION: Patients received either once weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. MAIN OUTCOME MEASURES: At 3 months, the primary end point was a composite of improvements in proptosis, lid fissure width, and rate of diplopia in primary gaze, visual acuity, eye muscle thickness, and patient's quality of life. RESULTS: Intravenous glucocorticoid therapy resulted in rapid, significant, and sustained improvement. At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the iv group. TSH receptor antibody titers decreased during iv steroid administration (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001). Additional treatment was required less frequently in the iv group. Intravenous steroids were safe, with different rates of adverse events between the two groups (P < 0.001). CONCLUSIONS: In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.

Administration, Oral↗

PubMed2005

Immunoregulatory and susceptibility genes in thyroid and polyglandular autoimmunity.

The etiology of autoimmune thyroid diseases (AITD) is based on genetic and nongenetic factors. Genome-wide screening and linkage analyses have identified several chromosomal regions that are linked to AITD. These are HT-1 (on chromosome 13q33) and HT-2 (chromosome 12q22) for Hashimoto's thyroiditis (HT), and GD-1 (chromosome 14q31), GD-2 (chromosome 20q11.2), and GD-3 (chromosome Xq21) for Graves' disease (GD). Several genes have been proposed as susceptibility or immunoregulatory genes. Most promising genes are those of the major histocompatibility complex (MHC) complex (chromosome 6), the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene (chromosome 2), the CD40 (chromosome 20), the thyroglobulin gene (chromosome 8), and the autoimmune regulator gene (chromosome 21). This review summarizes evidence for pathogenetic involvement of several of these genes in various forms of autoimmune thyropathies. Most genetic data refer to GD, whereas less data are available for HT and thyroid-associated ophthalmopathy. Scarce data refer to AITD within the autoimmune polyglandular syndromes I and II. The realization of family studies in large samples from different populations might provide further insight in the genetic contribution to AITD. Data are also needed on the interaction among susceptibility genes. Finally, additional functional studies are warranted to clarify the possible role of allelic variants in the underlying pathogenic mechanisms of AITD.

Autoimmune Diseases↗

PubMed2004

Contribution of genetic and environmental factors to variation in body compartments--a twin study in adults.

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.

Adult↗

PubMed2003

Reliability and variability of bioimpedance measures in normal adults: effects of age, gender, and body mass.

This study aimed to analyze the reliability and evaluate the causes of variability of bioimpedance parameters. Direct measures were analyzed because they are not affected by inappropriate prediction models. Resistance (R), reactance (Xc), and phase angle (PA) were determined at three fixed frequencies (5, 50, and 100 kHz) in 653 normal Germans (244 males and 409 females), aged 20-90 years, using a phase-sensitive whole-body tetrapolar bioimpedance analyzer (BIA 2000-M, Data Input, Germany). From these values, six bioimpedance ratios were calculated (R(5)/R(50), R(5)/R(100), Xc(5)/Xc(50), Xc(5)/Xc(100), PA(5)/PA(50), and PA(5)/PA(100)). Reliability of duplicate measurements, as determined by technical error, is high. ANOVA for repeated measurements yields a significant frequency main effect (within-subjects factor) and significant effects of age and gender (between-subject factors) on variation of resistance, reactance, and phase angle. Multiple regression analyses indicate independent effects of age, gender, and body mass index on variability of resistance, reactance, and phase angle at the three frequencies. Gender primarily influences variation in resistance (smaller values in males), whereas age mainly affects variations in reactance and phase angle (smaller values in older adults). Obesity is associated with smaller resistance (at all frequencies) and smaller reactance (high frequencies), but larger phase-angle values (low frequency). The study shows that variability of direct bioimpedance measures depends on age, gender, and body mass characteristics of the study population. The potential benefit for using both low and high frequencies in R measures is to differentiate between extra- and intracellular fluid spaces, which may be altered during human growth and aging.

Adult↗

PubMed2003

Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up.

Polyglandular autoimmune syndromes (PAS) are rare polyendocrinopathies characterized by the failure of several endocrine glands as well as nonendocrine organs, caused by an immune-mediated destruction of endocrine tissues. This article summarizes extensive clinical, epidemiological, serological, and genetic data of a large collective of patients with PAS (n = 360). Since 1988, more than 15,000 adult patients with endocrine diseases have been screened at the endocrine center of the Mainz University, and 151 of 360 patients with PAS have regularly been followed. Type 1 diabetes, Graves' disease, Hashimoto thyroiditis, Addison's disease, vitiligo, alopecia, hypogonadism, and pernicious anemia were observed in 61%, 33%, 33%, 19%, 20%, 6%, 5%, and 5%, respectively. The most common disease combination was type 1 diabetes and autoimmune thyroid disease. In most patients, type 1 diabetes was the first manifestation of PAS (48%). The longest time intervals between manifestations of the first and second immune endocrinopathies occurred between type 1 diabetes and thyroid disease (13.3 +/- 11.8 yr) and between vitiligo and thyroid disease (16.3 +/- 13.3 yr), but a shorter time interval was observed between Addison's and thyroid diseases. Of the 471 patients with type 1 diabetes screened, 83 (17.6%) were positive for PAS. Subsequently, sera of 126 patients with PAS, 287 with type 1 diabetes, and 303 matched controls were compared for human leukocyte antigens. Patients with PAS had significantly higher frequencies of the human leukocyte antigens A24, A31, B8, B51, B62, DR3, and DR4 (relative risk, 2.35, 2.74, 2.47, 7.17, 2.22, 1.94, and 2.46) vs. controls, and for A31, B15, B52, B55, DR2, DR11, and DR13 (relative risk, 2.51, 7.96, 3.99, 5.36, 4.46, 2.89, and 3.26) vs. type 1 diabetes patients without PAS. In conclusion, patients with autoimmune endocrine disease should be followed on a regular basis. In subjects at risk for PAS, functional screening every 3 yr is warranted. If clinical disease is present, serological measurement of organ-specific antibodies should follow.

Adult↗

PubMed2002

[Randomized, double-blind crossover study of bioavailability of levothyroxine].

OBJECTIVE: The synthetic thyroid hormone levothyroxine-sodium (LT4) is still the treatment of choice to replace thyroid hormone deficiency in hypothyroidism, and for adjuvant treatment of euthyroid goiter. A change of LT4 preparations during treatment may lead to major changes of thyroid hormone levels. In this study, we compared the bioavailability of two LT4 preparations, L-Thyroxin Henning 100 and Eferox 100. PATIENTS AND METHODS: In a double-blind trial, 60 euthyroid volunteers were randomly assigned to two treatment groups. Over a period of 2 weeks, each group received 0.1 mg/d of the different preparations according to a "crossover design". To monitor the efficacy of the different drugs, baseline serum thyrotropin (TSH) and free thyroxine (fT4) levels were measured with the help of immunoenzyme tests. RESULTS: Compared to Eferox, L-Thyroxin Henning led to continuously higher fT4 levels (p = 0.0004). The area under the concentration-time curve (AUC) of fT4 also confirmed this highly significant difference. With respect to the influencing factors, a higher bioavailability in men compared to women (p = 0.004) was noted. Also, the increase of body weight was related to a lower bioavailability (p = 0.002). Regarding the baseline TSH serum levels, a reduction of 70% in the L-Thyroxin Henning group versus only 56% in the Eferox group was noted after a period of 14 days. Clinical symptoms of hyperthyroidism were not observed in the volunteers under both substances. CONCLUSION: In this study, L-Thyroxin Henning 100 showed a significantly higher bioavailability than Eferox 100 (p = 0.001). According to these findings, we do recommend regular measurements of serum TSH and fT4 levels when changing LT4 preparations of different brands, to cope with metabolic decompensation by using a new LT4 dosage.

Adult↗

PubMed2002

Evaluation of different methods for assessing intracellular fluid in healthy older people: a cross-validation study.

OBJECTIVES: To cross-validate existing anthropometric and bioimpedance equations to establish their validity and accuracy for estimating intracellular water (ICW) in healthy older Germans and to develop a new equation with improved accuracy and precision for predicting ICW from multifrequency bioimpedance analysis (MFBIA). DESIGN: Cross-validation study. SETTING: University of Mainz. PARTICIPANTS: One hundred fifty-five healthy volunteers aged 60 to 80 years (77 men, 78 women; mean ages +/- standard deviation 67.7 +/- 4.8 and 68.6 +/- 5.5 years, respectively). MEASUREMENTS: ICW was measured by whole-body counting of (40)potassium ((40)K) ((40)K method) as the reference method and compared by cross-validation techniques against five existing bioimpedance and three anthropometric prediction equations. A new equation for estimating ICW from MFBIA was developed using the (40)K method as criterion method. RESULTS: Compared with the (40)K method, the existing bioimpedance and anthropometric equations showed large prediction errors in ICW estimates for older men (-32.3% to +37.7%) and women (-34.2% to +26.6%), depending significantly and positively on ICW volume and inversely on weight. A new equation for estimating ICW from MFBIA was developed (R(2)=0.933, standard error of the estimate (SEE)=0.92 L) involving phase angle at 5 kHz, impedance, height, and gender, with data from 100 subjects chosen at random. Cross-validation on an independent group (n=55, R(2)=0.958, SEE=0.68 L) showed no significant bias (0.013 +/- 1.52 L). CONCLUSIONS: Published bioimpedance and anthropometric prediction equations are not applicable to older Germans because they might be population-specific. The bioimpedance equation of the manufacturer of the bioimpedance analyzer used in this study provides accurate estimates of ICW for normal weight, but not overweight, older men. The newly developed equation improves accuracy and precision of ICW estimates by MFBIA.

Aged↗

PubMed2002

Functional and postural lateral preferences in humans: interrelations and life-span age differences.

This study aimed to provide data on lateral preferences among older subjects, to analyze age differences, and to determine interrelations between lateral preferences. Four functional preferences (handedness, footedness, eyedness, earedness) and three postural lateral preferences (hand-clasping, arm-folding, leg-crossing) were assessed in 628 Germans (252 men, 376 women) aged between 19 and 90 years. Sex differences, age differences, and associations between lateralities were analyzed applying chi-square tests. Logistic regression analyses considering age, sex, and interactions between variables were applied to analyze combined effects on laterality measures. Right-sided preference for handedness, footedness, eyedness, earedness, and leg-crossing characterized 86.8%, 77.1%, 70.9%, 67.8%, and 56.6%, respectively, of subjects, while a left-sided preference for hand-clasping and arm-folding characterized 56.4% and 60.2%, respectively, of all participants. Results are within the range of other populations. Only footedness differed between the sexes: there were more left-footed men. Older cohorts showed a rightward shift in handedness, eyedness, earedness, and leg-crossing, the opposite for arm-folding. No age-related differences exist in footedness or hand-clasping. Logistic regression models indicate no interaction between age and sex for each laterality measure. The four functional lateralities are significantly interrelated. All also are positively associated with leg-crossing. Conversely, the postural lateralities generally are not correlated, although leg-crossing and arm-folding are, inversely. The observed relationships among lateralities support the hypothesis that handedness, footedness, leg-crossing, and earedness might be aspects of a larger phenotype that is independent of hand-clasping and arm-folding.

Adult↗

PubMedDate not supplied

Comparison of bipolar and tetrapolar impedance techniques for assessing fat mass.

Whole body fat mass (BF) can be predicted by different bioimpedance (BIA) techniques measuring the whole body (tetrapolar hand-to-foot technique, HF), lower body (bipolar foot-to-foot technique, FF), or upper body (bipolar hand-to-hand technique, HH). This study analyzed 146 healthy volunteers (age 18-84 years) for whether these three techniques differ in their estimates of BF, and whether sex and age of the subjects influence estimates of BF. Reproducibility of the techniques was tested by calculating the technical error (TE). Effects of BIA technique, sex, and age on predicted BF were analyzed with ANOVA for repeated measurements in a mixed effect design. Results showed high reproducibility for the three BIA techniques (TE = 0.01-0.03 kg). ANOVA indicated interactions between BIA technique and sex (P = 0.035), BIA technique and age (P < 0.001), as well as effects of sex (P = 0.004) and age (P = 0.001) on variation in BF. The HH technique gave the highest values for BF in males, but lowest values in females, whereas the reverse was found for the FF technique. The HH technique yielded the lowest values for BF in young adults, but highest values in older ones. The reverse was noted for the FF technique. The data suggest that the observed differences in the three BIA techniques in predicting BF reflect sex differences and age-associated changes in body fat patterning. Therefore, the whole body impedance method is preferred over the HH and FF techniques due to the interactions with sex and age.

Adolescent↗

PubMedDate not supplied

Validation of different bioimpedance analyzers for predicting cell mass against whole-body counting of potassium (40K) as a reference method.

This study compared two different tetrapolar bioimpedance (BIA) devices for estimating body cell mass (BCM), validated them against whole-body counting of (40)K (TBK method), and developed improved prediction equations for estimating BCM from BIA. In 50 healthy volunteers (age 23-65 years, BMI 18.6-27.7 kg/m(2)), BCM was estimated with the BIA devices Nutriguard-M (Data Input, Germany) and Soft-Tissue-Analyzer-STA (Akern, Italy) and by the TBK method. Methods were compared by the Bland-Altman procedure. New prediction equations for BCM were developed by multiple stepwise regression analysis based on a single BIA parallel model. The Akern device gives similar mean estimates of BCM compared to the Data Input device in males (33.5 vs. 33.3 kg, P = 0.789), but higher values in females (24.6 vs. 22.8 kg; P < 0.001). Both BIA devices overestimate mean BCM relative to the TBK method; in males by 5.0 kg (Data Input, P < 0.001) and 5.1 kg (Akern, P < 0.001); in females by 2.3 kg (Data Input, P < 0.001) and 4.1 kg (Akern, P < 0.001). Limits of agreement between BIA and TBK methods are for males +/-4.99 kg (Data Input) and +/-7.16 kg (Akern); for females, +/-4.69 kg (Data Input) and +/-4.12 kg (Akern). New equations were developed for estimating BCM for both BIA analyzers (Data Input, R(2) = 0.91, SEE = 1.46 kg; Akern, R(2) = 0.90, SEE = 1.48 kg). Since estimates of BCM by the present BIA devices do not differ in males, they might be interchangeable. This does not hold true for females. Because both BIA devices overestimate BCM, the newly developed device-specific equations which reduce bias and limits of agreement should be applied.

Adult↗